dbSNP rs8112982: FBN3:c.6031+141G>A (chr19-8091324-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032447.5(FBN3):c.6031+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,149,846 control chromosomes in the GnomAD database, including 1,446 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.059 ( 869 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 577 hom. )

Consequence

FBN3
NM_032447.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0580

Publications

1 publications found

Variant links:

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

FBN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5 link	c.6031+141G>A		intron_variant	Intron 48 of 63	ENST00000600128.6	NP_115823.3	Q75N90A8KAY2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FBN3	ENST00000600128.6 link	c.6031+141G>A	intron_variant	Intron 48 of 63	1	NM_032447.5	ENSP00000470498.1	Q75N90
FBN3	ENST00000270509.6 link	c.6031+141G>A	intron_variant	Intron 47 of 62	1		ENSP00000270509.2	Q75N90
FBN3	ENST00000601739.5 link	c.6031+141G>A	intron_variant	Intron 48 of 63	1		ENSP00000472324.1	Q75N90
FBN3	ENST00000651877.1 link	c.6157+141G>A	intron_variant	Intron 48 of 63			ENSP00000498507.1	A0A494C0D8

Frequencies

GnomAD3 genomes

AF:

0.0593

AC:

9025

AN:

152138

Hom.:

864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0207

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0464

GnomAD4 exome

AF:

0.00844

AC:

8415

AN:

997590

Hom.:

577

AF XY:

0.00832

AC XY:

4181

AN XY:

502748

show subpopulations

African (AFR)

AF:

0.203

AC:

4715

AN:

23254

American (AMR)

AF:

0.0139

AC:

409

AN:

29352

Ashkenazi Jewish (ASJ)

AF:

0.0000561

AC:

AN:

17828

East Asian (EAS)

AF:

0.0184

AC:

683

AN:

37196

South Asian (SAS)

AF:

0.0228

AC:

1424

AN:

62428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41994

Middle Eastern (MID)

AF:

0.0107

AC:

AN:

4590

European-Non Finnish (NFE)

AF:

0.000563

AC:

415

AN:

736644

Other (OTH)

AF:

0.0162

AC:

719

AN:

44304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

372

745

1117

1490

1862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0595

AC:

9056

AN:

152256

Hom.:

869

Cov.:

AF XY:

0.0582

AC XY:

4335

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.201

AC:

8348

AN:

41490

American (AMR)

AF:

0.0207

AC:

317

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0235

AC:

122

AN:

5190

South Asian (SAS)

AF:

0.0230

AC:

111

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68036

Other (OTH)

AF:

0.0464

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

384

768

1152

1536

1920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0409

Hom.:

Bravo

AF:

0.0674

Asia WGS

AF:

0.0350

AC:

123

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.1

(source)

DANN

Benign

0.39

PhyloP100

0.058

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over